A nucleotide-based drug protects against glutamate- and MPP+ -induced neurotoxicity

Abstract

Nucleo CMP Forte® is a nucleotide-based drug consisting of cytidinemonophosphate, uridinemonophosphate, uridin-ediphosphate and uridinetriphosphate. It has been prescribed for peripheral nervous system disorders, such as lum-bosciatalgia, diabetic or alcoholic polyneuropathy, or trigeminal neuralgia. Its effects on brain pathologies has re-ceived little attention. We examined its neuroprotective effects on cell toxicity induced by glutamate excitotoxicity or by 1-methyl-4-phenyl-pyridinium (MPP+), an in vitro cell model of Parkinson’s disease. We used the human dopaminergic cell line SH-SY5Y and a primary culture of rat cortical cells pre-treated with the drug for 24 hours and then exposed to MPP+ or glutamate at a range of concentrations. Cell viability was measured at different times. Nucleo CMP Forte® pre-treatment significantly increased the rate of cell division in SH-SY5Y cells, as well as the synthesis of triglycerides and phospholipids. More interestingly, drug pre-treatment significantly reduced MPP+- and glutamate-induced cell death in SH-SY5Y cells and in rat cortical cells. These results indicate that the nucleotides included in Nucleo CMP Forte® are promising therapeutic molecules for the prevention of neuronal death in brain caused by focal ischemia, Parkinson’s disease or other neurodegenerative pathologies.